Intradermal SynCon® Ebola GP DNA Vaccine Is Temperature Stable and Safely Demonstrates Cellular and Humoral Immunogenicity Advantages in Healthy Volunteers.

BACKGROUND: Nonlive vaccine approaches that are simple to deliver and stable at room temperature or 2-8°C could be advantageous in controlling future Ebola virus (EBOV) outbreaks. Using an immunopotent DNA vaccine that generates protection from lethal EBOV challenge in small animals and nonhuman primates, we performed a clinical study to evaluate both intramuscular (IM) and novel intradermal (ID) DNA delivery. METHODS: Two DNA vaccine candidates (INO-4201 and INO-4202) targeting the EBOV glycoprotein (GP) were evaluated for safety, tolerability, and immunogenicity in a phase 1 clinical trial. The candidates were evaluated alone, together, or in combination with plasmid-encoded human cytokine interleukin-12 followed by in vivo electroporation using either the CELLECTRA® IM or ID delivery devices. RESULTS: The safety profile of all 5 regimens was shown to be benign, with the ID route being better tolerated. Antibodies to EBOV GP were generated by all 5 regimens with the fastest and steepest rise observed in the ID group. Cellular immune responses were generated with every regimen. CONCLUSIONS: ID delivery of INO-4201 was well tolerated and resulted in 100% seroreactivity after 2 doses and elicited interferon-γ T-cell responses in over 70% of subjects, providing a new approach for EBOV prevention in diverse populations. Clinical Trials Registration. NCT02464670.

Microstructure Design of High-Entropy Alloys Through a Multistage Mechanical Alloying Strategy for Temperature-Stable Megahertz Electromagnetic Absorption.

Developing megahertz (MHz) electromagnetic wave (EMW) absorption materials with broadband absorption, multi-temperature adaptability, and facile preparation method remains a challenge. Herein, nanocrystalline FeCoNiCr0.4Cu0.2 high-entropy alloy powders (HEAs) with both large aspect ratios and thin intergranular amorphous layers are constructed by a multistage mechanical alloying strategy, aiming to achieve excellent and temperature-stable permeability and EMW absorption. A single-phase face-centered cubic structure with good ductility and high crystallinity is obtained as wet milling precursors, via precisely controlling dry milling time. Then, HEAs are flattened to improve aspect ratios by synergistically regulating wet milling time. FeCoNiCr0.4Cu0.2 HEAs with dry milling 20 h and wet milling 5 h (D20) exhibit higher and more stable permeability because of larger aspect ratios and thinner intergranular amorphous layers. The maximum reflection loss (RL) of D20/SiO2 composites is greater than - 7 dB with 5 mm thickness, and EMW absorption bandwidth (RL < - 7 dB) can maintain between 523 and 600 MHz from - 50 to 150 °C. Furthermore, relying on the "cocktail effect" of HEAs, D20 sample also exhibits excellent corrosion resistance and high Curie temperature. This work provides a facile and tunable strategy to design MHz electromagnetic absorbers with temperature stability, broadband, and resistance to harsh environments.

Achieving Ultrahigh Energy-Storage Density with Excellent Thermal Stability in Sr0.7Bi0.2TiO3-Based Relaxors via Polarization Behavior Modulation.

Dielectric capacitors possessing the inherent superiorities of high power density and ultrafast charge-discharge speed make their utilization in energy-storage devices extremely propitious, although the relatively low recoverable energy-storage density (Wrec) may impede their applications. In this work, unlike the mainstream approach of destroying long-range ferroelectric/antiferroelectric order and inducing relaxor properties to achieve a high Wrec value, we have selected end members with a high polarization gene to promote the polarization behavior of the typical relaxor Sr0.7Bi0.2TiO3. Therefore, an ultrahigh Wrec ∼ 8 J/cm3 and a superior efficiency (η) ∼ 91% are accomplished in the 0.98[0.56(Sr0.7Bi0.2)TiO3-0.44(Bi0.5Na0.5)TiO3]-0.02 Bi(Mg0.5Ti0.5)O3 sample. The achieved Wrec value is record high in Sr0.7Bi0.2TiO3-based systems as far as we know. The polarization-enhancement behavior can be explained by the phase field simulation results, phase content variance in X-ray diffraction Rietveld refinement, hardening trend in Raman spectroscopy, domain morphology, and local symmetry in transmission electron microscope analysis. Meanwhile, the ceramic possesses excellent thermal stability (ΔWrec < 12.7% and Δη < 10.4%, -50-200 °C), frequency (ΔWrec < 2.69% and Δη < 2.06%, 0.5-500 Hz), and fatigue-resistant stability (ΔWrec < 0.08% and Δη < 0.2%, up to 1 × 105 cycles). Accordingly, this work proposes a design idea to tailor the polarization behavior and energy-storage properties of typical relaxors.

An AAV-based, room-temperature-stable, single-dose COVID-19 vaccine provides durable immunogenicity and protection in non-human primates.

The SARS-CoV-2 pandemic has affected more than 185 million people worldwide resulting in over 4 million deaths. To contain the pandemic, there is a continued need for safe vaccines that provide durable protection at low and scalable doses and can be deployed easily. Here, AAVCOVID-1, an adeno-associated viral (AAV), spike-gene-based vaccine candidate demonstrates potent immunogenicity in mouse and non-human primates following a single injection and confers complete protection from SARS-CoV-2 challenge in macaques. Peak neutralizing antibody titers are sustained at 1 year and complemented by functional memory T cell responses. The AAVCOVID vector has no relevant pre-existing immunity in humans and does not elicit cross-reactivity to common AAVs used in gene therapy. Vector genome persistence and expression wanes following injection. The single low-dose requirement, high-yield manufacturability, and 1-month stability for storage at room temperature may make this technology well suited to support effective immunization campaigns for emerging pathogens on a global scale.

Flexible, Temperature-Resistant, and Fatigue-Free Ferroelectric Memory Based on Bi(Fe0.93Mn0.05Ti0.02)O3 Thin Film.

A recent hot-spot topic for flexible and wearable devices involves high-performance nonvolatile ferroelectric memories operating under compressive or tensile mechanical deformations. This work presents the direct fabrication of a flexible (Mn,Ti)-codoped multiferroic BiFeO3 film capacitor with Pt bottom and Au top electrodes on mica substrate. The fabricated polycrystalline Bi(Fe0.93Mn0.05Ti0.02)O3 film on mica exhibits superior ferroelectric switching behavior with robust saturated polarization ( Ps ∼ 93 µC/cm2) and remanent polarization ( Pr ∼ 66 µC/cm2) and excellent frequency stability (1-50 kHz) and temperature resistance (25-200 °C), as well as reliable long-lifetime operation. More saliently, it can be safely bent to a small radius of curvature, as low as 2 mm, or go through repeated compressive/tensile mechanical flexing for 103 bending times at 4 mm radius without any obvious deterioration in polarization, retention time at 105 s, or fatigue resistance after 109 switching cycles. These findings demonstrate a novel route to designing flexible BiFeO3-based ferroelectric memories for information storage and data processing, with promising applications in next-generation smart electronics.

Research and Analysis of MEMS Switches in Different Frequency Bands.

Due to their high isolation, low insertion loss, high linearity, and low power consumption, microelectromechanical systems (MEMS) switches have drawn much attention from researchers in recent years. In this paper, we introduce the research status of MEMS switches in different bands and several reliability issues, such as dielectric charging, contact failure, and temperature instability. In this paper, some of the following methods to improve the performance of MEMS switches in high frequency are summarized: (1) utilizing combinations of several switches in series; (2) covering a float metal layer on the dielectric layer; (3) using dielectric layer materials with high dielectric constants and conductor materials with low resistance; (4) developing MEMS switches using T-match and π-match; (5) designing MEMS switches based on bipolar complementary metal⁻oxide⁻semiconductor (BiCMOS) technology and reconfigurable MEMS' surfaces; (6) employing thermal compensation structures, circularly symmetric structures, thermal buckle-beam actuators, molybdenum membrane, and thin-film packaging; (7) selecting Ultra-NanoCrystalline diamond or aluminum nitride dielectric materials and applying a bipolar driving voltage, stoppers, and a double-dielectric-layer structure; and (8) adopting gold alloying with carbon nanotubes (CNTs), hermetic and reliable packaging, and mN-level contact.

Characterization and thermal inactivation kinetics of highly thermostable ramie leaf ß-amylase.

We characterized ramie leaf ß-amylase, and determined its thermostability and kinetic parameters. The enzyme was purified 53-fold using ammonium sulfate fractionation (40-60% saturation), anion exchange chromatography on DEAE-cellulose and gel permeation chromatography on Superdex-200. The purified enzyme was identified as ß-amylase with molecular mass of 42kD. The enzyme displayed Km and kcat values for soluble potato starch of 1.1mg/mL and 7.8s-1, respectively. The enzyme had a temperature optimum of 65°C, and its activity at 70°C was 92% of that at the optimal temperature after a 15-min incubation. Furthermore, enzyme activity was stable during treatment at 55°C for 60min but was inactivated rapidly at >75°C. This thermal behavior indicates that ramie leaf ß-amylase has excellent intermediate temperature-stable enzyme properties for the baking and bio-industries. Inactivation of the enzyme followed first-order kinetics in the range of 55-80°C. The enthalpy change of thermal inactivation (ΔH‡), ΔG‡, and ΔS‡ were 237.2kJ/mol, 107.7kJ/mol, and 0.39kJ/molK at 333K, respectively. The D-value at 65°C (=110min) and the z-value (=9.4°C) are given for food processing.

Room temperature stable carbetocin for the prevention of postpartum haemorrhage during the third stage of labour in women delivering vaginally: study protocol for a randomized controlled trial.

BACKGROUND: Postpartum haemorrhage (PPH) is the leading cause of maternal mortality in low-income countries and contributes to nearly a quarter of maternal deaths globally. The current available interventions for prevention of postpartum haemorrhage, oxytocin and carbetocin, are limited by their need for refrigeration to maintain potency, as the ability to maintain a cold chain across the drug distribution and storage network is inconsistent, thus restricting their use in countries with the highest burden of maternal mortality. We describe a randomized, double-blind non-inferiority trial comparing a newly developed room temperature stable formulation of carbetocin to the standard intervention (oxytocin) for the prevention of PPH after vaginal birth. METHODS/DESIGN: Approximately 30,000 women delivering vaginally will be recruited across 22 centres in 10 countries. The primary objectives are to evaluate the non-inferiority of room temperature stable carbetocin (100 µg intramuscular) versus oxytocin (10 IU intramuscular) in the prevention of PPH and severe PPH after vaginal birth. The primary endpoints are blood loss ≥500 mL or the use of additional uterotonics (composite endpoint required by drug regulatory authorities) and blood loss ≥1,000 mL (WHO requirement). Non-inferiority will be assessed using a two-sided 95 % confidence interval for the relative risk of the above endpoints for room temperature stable carbetocin versus oxytocin. The upper limit of the two-sided 95 % confidence interval for the relative risk for the composite endpoint of blood loss ≥500 mL or the use of additional uterotonics, and for the endpoint of blood loss ≥1,000 mL, will be compared to a non-inferiority margin of 1.16 and 1.23, respectively. If the upper limit is below the corresponding margin, non-inferiority will have been demonstrated. The safety analysis will include all women receiving treatment. Safety and tolerability will be assessed by a review of adverse events, by conducting inferential testing with significance levels for between-group comparisons. DISCUSSION: If the results of the study show that room temperature stable carbetocin is a safe and effective alternative to oxytocin, this could have a substantial impact on the prevention of postpartum haemorrhage and maternal survival worldwide. TRIAL REGISTRATION: ACTRN12614000870651 (14 August 2014).